Primary Human Retinal Microvascular Endothelial Cells (ACBRI 181) are initiated by elutriation of dispase dissociated normal human retinal tissue.

Cell Initiation

These cells were originated using Cell Systems Complete Serum-Free Medium (SF-4Z0-500), and subsequently grown and passaged in Cell Systems Complete Medium (4Z0-500). They are available at Passage 3 [< 12 cumulative population doublings] cryopreserved in Cell Systems Cell Freezing Medium™ (4Z0-705). This vial will initiate a Passage 4 cell culture in a 75cm² flask. Each vial contains more than 1 x 10⁶cells.

In addition to cryopreserved vial, these cells are also available in 25cm² and 75cm² proliferating cell culture flasks (US domestic market only).

Click For Current Applications and Assays Using Cell Systems Primary Human Retinal Microvascular Endothelial Cells (ACBRI 181)

Companion Products

Each vial of cells is shipped to customer with Bac-Off® (antibiotic), and CultureBoost™ (animal derived growth factors) or CultureBoost-R (human recombinant growth factors)

These cells are qualified for use with:

Complete Classic Medium Kit with Serum and CultureBoost™

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The System™

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Passage Reagent Group™

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Standard Tests

TEST	RESULTS
HIV Serologic Test (donor level HIV AB EIA)	Negative
HIV PCR Test (frozen cell pool by CLIA Licensed Clinical Lab)	Negative
Hepatitis B (HBV) and Hepatitis C (HCV) PCR Test (at frozen cell level)	Negative
Test of frozen cells for Mycoplasma spp. (ATCC method by CLIA Licensed Clinical Lab)	Negative

Miscellaneous Tests

TEST	RESULTS
Cytoplasmic VWF / Factor VIII	> 95% positive by immunofluorescence
Cytoplasmic uptake of Di-I-Ac-LDL	> 95% positive by immunofluorescence
Cytoplasmic CD31	> 95% positive by immunofluorescence
GFAP (Glial Fibrillary Acidic Protein)	< 1% by immunofluorescence
Glutamine Synthetase	< 1% by immunofluorescence
NG2 (Neural/Glial Antigen 2)	< 1% by immunofluorescence
PDGFR-beta (Platelet Derived Growth Factor Receptor beta)	< 1% by immunofluorescence

Characterization in Peer-Reviewed Literature

Cell Systems Primary Human Retinal Microvascular Endothelial Cells (HREC) express hallmark endothelial cell markers such as PECAM1/CD31 (A), von Willebrand Factor (B), and VE-Cadherin/CDH5 (C); and treatment with TNF-alpha induces expression of endothelial-cell specific protein E-selectin (D) as measured by mRNA abundance. In contrast, the widely-used immortalized cell line RF/6A does not share hallmark endothelial cell characteristics. Modified with permission from Figures 1-3, Makin et al. IOVS (2018) 59:5795-5802.

Citations:

"Downregulation of CKS1B restrains the proliferation, migration, invasion and angiogenesis of retinoblastoma cells through the MEK/ERK signaling pathway" Zeng et al. International Journal of Molecular Medicine,  2019

"Co-culture of human induced pluripotent stem cell-derived retinal pigment epithelial cells and endothelial cells on double collagen-coated honeycomb films" Calejo et al. Acta Biomater, 2019

List of 2018-2019 Citations, organized by application and assay type

"Myeloid SOCS3 Deficiency Regulates Angiogenesis via Enhanced Apoptotic Endothelial Cell Engulfment" Korovina et al. J Innate Immunity, 2019
"Endomucin restores depleted endothelial glycocalyx in the retinas of streptozotocin-induced diabetic rats" Niu et al. FASEB Journal, 2019
"Epigenetic Modifications Compromise Mitochondrial DNA Quality Control in the Development of Diabetic Retinopathy" Mohammad et al. IOVS, 2019
"Annexin A2 upregulation protects human retinal endothelial cells from oxygen‑glucose deprivation injury by activating autophagy" Jiang & Xu, Experimental and Therapeutic Medicine, 2019

"MicroRNA-34a (miR-34a) mediates retinal endothelial cell premature senescence through mitochondrial dysfunction and loss of antioxidant activities" Thounaojam et al, Antioxidants, 2019

"Angiopoietin 1 attenuates interleukin-6-induced endothelial cell permeability through SHP-1" Yun et al, BBRC, 2019

"GRP78 translocation to the cell surface and O-GlcNAcylation of VE-Cadherin contribute to ER stress-mediated endothelial permeability" Lenin et al. Scientific Reports, 2019

"Functional regulation of an oxidative stress mediator, Rac1, in diabetic retinopathy" Mohammad et al. Molecular Neurobiology, 2019

"Development and characterization of an in vitro system of the human retina using cultured cell lines" Churm et al. Clinical & Experimental Ophthalmology, 2019

"RANKL blockade suppresses pathological angiogenesis and vascular leakage in ischemic retinopathy" Ock et al. BBRC, 2019

"Pro-angiogenic ginsenosides F1 and Rh1 inhibit vascular leakage by modulating NR4A1" Kang et al. Scientific Reports, 2019

"ASK1 induces retinal microvascular endothelial cell apoptosis through ER stress-associated pathway" Zou et al. Intl J Clinical Experimental Pathology, 2019

"Modulation of the p75 neurotrophin receptor using LM11A-31 prevents diabetes-induced retinal vascular permeability in mice via inhibition of inflammation and the RhoA kinase pathway" Elshaer et al. Diabetologia, 2019

"Serum miR‑338‑5p has potential for use as a tumor marker for retinoblastoma" Zhou and Li, Oncology Letters, 2019

"Enhancing retinal endothelial glycolysis by inhibiting UCP2 promotes physiologic retinal vascular development in a model of retinopathy of prematurity" Han et al. IOVS, 2019

"Improvement in diabetic retinopathy through protection against retinal apoptosis in spontaneously diabetic Torii rats mediated by ethanol extract of Osteomeles schwerinae C.K. Schneid" Kim, Kim, Kim et al. Nutrients, 2019

"Mitochondrial fusion and maintenance of mitochondrial homeostasis in diabetic retinopathy" Duraisamy et al. BBA Molecular Basis of Disease, 2019

"MicroRNA-145 regulates pathological retinal angiogenesis by suppresion of TMOD3" Liu et al. Nucleic Acids, 2019

"Pro-angiogenic ginsenosides F1 and Rh1 inhibit vascular leakage by modulating NR4A1" Kang et al. Scientific Reports, 2019

"Three-dimensional tubule formation assay as therapeutic screening model for ocular microvascular disorders" Shariatzadeh et al. Nature: Eye, 2018

"RF/6A Chorioretinal Cells Do Not Display Key Endothelial Phenotypes" Makin et al. IOVS, 2018

"Epac1 deacetylates HMGB1 through increased IGFBP-3 and SIRT1 levels in the retinal vasculature" Jiang et al. Molecular Vision, 2018

"Vascular protection of DPP-4 inhibitors in retinal endothelial cells in in vitro culture" Li et al. International Immunopharmacology, 2018

"3-Hydroxypyruvate destabilizes hypoxia inducible factor and induces angiostasis" Singh et al. IOVS, 2018

"Adaptor protein p66Shc: a link between cytosolic and mitochondrial dysfunction in the development of diabetic retinopathy" Mishra et al. Antioxidants & Redox Signaling, 2018

"Interaction of palmitate and LPS regulates cytokine expression and apoptosis through sphingolipids in human retinal microvascular endothelial cells" Lu et al. Experimental Eye Research, 2018

"Activation of the sweet taste receptor T1R3 by sucralose attenuates VEGF-induced vasculogenesis in a cell model of the retinal microvascular endothelium" Lizunkova et al. Graefe's Archive for Clinical and Experimental Ophthalmology, 2018

"Activation of the Notch‑Nox4‑reactive oxygen species signaling pathway induces cell death in high glucose‑treated human retinal endothelial cells" Jiao et al. Molecular Medicine Reports, 2018

"YAP via interacting with STAT3 regulates VEGF-induced angiogenesis in human retinal microvascular endothelial cells" Zhu and Liu et al, Experimental Cell Research, 2018

"PKA regulates HMGB1 through activation of IGFBP-3 and SIRT1 in human retinal endothelial cells cultured in high glucose" Liu et al. Inflammation Research, 2018

"Effects of LY294002 on the function of retinal endothelial cell in vitro" Di and Chen, Intl J Ophthalmology, 2018

"miR-215 controls proliferation, invasion, and apoptosis of human retinoblastoma cells by regulating RB1 expression" Zhang et al. Intl J Experimental Clinical Medicine, 2018

"Expression of miR‑204 in pediatric retinoblastoma and its effects on proliferation and apoptosis of cancer cells" Ding and Lu, Oncology Letters, 2018

"Epigenetics and regulation of oxidative stress in diabetic retinopathy" A.J. Duraisamy et al. IOVS, 2018

"Tigecycline as a dual inhibitor of retinoblastoma and angiogenesis via inducing mitochondrial dysfunctions and oxidative damage" Xiong et al. Scientific Reports, 2018

"SiRNA silencing of VEGF, IGFs, and their receptors in human retinal microvascular endothelial cells" Nicolau et al. American J Translational Research, 2018

"Fenofibrate exerts protective effects in diabetic retinopathy via inhibition of the ANGPTL3 pathway" Wang et al. IOVS, 2018

"Critical role of endoplasmic reticulum stress in chronic endothelial activation−induced visual deficits in tie2‐tumor necrosis factor mice" Lenin et al. J Cellular Biochemistry, 2018

"miR15a regulates NLRP3 inflammasome proteins in the retinal vasculature" Curtiss et al. Experimental Eye Research, 2018

"CD140b (PDGFRβ) Signaling in Adipose-Derived Stem Cells Mediates Angiogenic Behavior of Retinal Endothelial Cells" Periasamy et al. Regenerative Engineering and Translational Medicine, 2018

"MicroRNA-145 attenuates high glucose-induced oxidative stress and inflammation in retinal endothelial cells through regulating TLR4/NF-κB signaling" Hui and Yin, Life Sciences, 2018

"Cross-inhibition of Norrin and TGF-β signaling modulates development of retinal and choroidal vasculature" Seitz et al, Retinal Cell Biology, 2018

"The benzodiazepine anesthetic midazolam prevents hyperglycemia-induced microvascular leakage in the retinas of diabetic mice" Lee, et al. FASEB Journal, 2018

"Intravitreal implantable magnetic micropump for on-demand VEGFR-targeted drug delivery" Wang et al. J Controlled Release, 2018

"Vitamin D3 protects against diabetic retinopathy by inhibiting high-glucose-induced activation of the ROS/TXNIP/NLRP3 inflammasome pathway" Lu et al. Journal of Diabetes Research, 2018

"Role of endoplasmic reticulum stress in 12/15-lipoxygenase-induced retinal microvascular dysfunction in a mouse model of diabetic retinopathy" Elmasry et al. Diabetologia, 2018

"Artemesia annua extract prevents glyoxal-induced cell injury in retinal microvascular endothelial cells during glaucoma" Jiang et al. Tropical Journal of Pharmaceutical Research, 2018

"Metformin suppresses retinal angiogenesis and inflammation in vitro and in vivo" Han et al. PLoS One, 2018

"Gastrodin inhibits high glucose‑induced human retinal endothelial cell apoptosis by regulating the SIRT1/TLR4/NF‑κBp65 signaling pathway" Zhang et al. Molecular Medicine Reports, 2018

"Profilin-1 mediates microvascular endothelial dysfunction in diabetic retinopathy through HIF-1α-dependent pathway" Ding et al. Int J Clin Exp Pathology, 2018

"DNA methylation—a potential source of mitochondria DNA base mismatch in the development of diabetic retinopathy" Mishra and Kowluru, Molecular Neurobiology, 2018

"Characterization of site-specific phosphorylation of NF-κB p65 in retinal cells in response to high glucose and cytokine polarization" Shi and Berger, Mediators of Inflammation, 2018

"Human retinal endothelial cells and astrocytes cultured on 3-D scaffolds for ocular drug discovery and development" Beharry et al. Prostaglandins and Other Lipid Mediators, 2018

"ANGPTL-4 induces diabetic retinal inflammation by activating Profilin-1" Lu et al. Experimental Eye Research, 2018

"Cathepsin D plays a role in endothelial–pericyte interactions during alteration of the blood–retinal barrier in diabetic retinopathy" Monickaraj et al. FASEB Journal, 2018

"Beta-adrenergic receptor agonists attenuate pericyte loss in diabetic retinas through Akt activation" Yun et al. FASEB Journal, 2018

"miRNA15a regulates insulin signal transduction in the retinal vasculature" Jiang et al. Cellular Signalling, 2018

"miR-539-5p inhibits experimental choroidal neovascularization by targeting CXCR7" Feng et al. FASEB Journal, 2018

"MnTBAP or catalase is more protective against oxidative stress in human retinal endothelial cells exposed to intermittent hypoxia than their co-administration" Quan et al, Reactive Oxygen Species, 2017

"Calcium influx through TRPV4 channels modulates the adherens contacts between retinal microvascular endothelial cells" Phuong et al. J Physiology, 2017

"MicroRNA‐containing extracellular vesicles released from endothelial colony‐forming cells modulate angiogenesis during ischaemic retinopathy" Dellett et al. Journal of Cellular and Molecular Medicine, 2017

"Hyperhomocysteinemia alters retinal endothelial cells barrier function and angiogenic potential via activation of oxidative stress" Mohamed et al. Scientific Reports, 2017

"Zika virus infection of cellular components of the blood-retinal barriers: implications for viral associated congenital ocular disease" Roach and Alcendor, Journal of Neuroinflammation, 2017

"Activation of the TXNIP/NLRP3 inflammasome pathway contributes to inflammation in diabetic retinopathy: a novel inhibitory effect of minocycline" Chen et al. Inflammation Research, 2017

"Contacting co-culture of human retinal microvascular endothelial cells alters barrier function of human embryonic stem cell derived retinal pigment epithelial cells" Skottman et al. Experimental Cell Research, 2017

"AAV-CRISPR/Cas9–mediated depletion of VEGFR2 blocks angiogenesis in vitro" Wu et al. IOVS, 2017

"Association of HMGB1 with oxidative stress markers and regulators in PDR" Abu El-Asrar and Alam et al. Molecular Vision, 2017

"STAT3-mediated activation of miR-21 is involved in down-regulation of TIMP3 and neovascularization in the ischemic retina" Gutsavea et al. Oncotarget, 2017

"Crosstalk between histone and DNA methylation in regulation of retinal matrix metalloproteinase-9 in diabetes" Duraisamy et al. IOVS, 2017

"Therapeutic effect of novel single-stranded RNAi agent targeting periostin in eyes with retinal neovascularization" Nakama et al. Molecular Therapy - Nucleic Acids, 2017

"Zika virus infects cells lining the blood-retinal barrier and causes chorioretinal atrophy in mouse eyes" Singh et al. JCI Insight, 2017

"Phenotype-based discovery of 2-[(E)-2-(Quinolin-2-yl)vinyl)phenol as a novel regulator of ocular angiogenesis" Reynolds et al, J Biological Chemistry, 2016

"A novel angiogenic peptide, ΔADT: A truncated adrenotensin peptide revealed by secretory peptidome analysis of human retinal pericytes" Okumura et al. BioScience Trends, 2016

"miR-146a attenuates inflammatory pathways mediated by TLR4/NF-κB and TNFα to protect primary human retinal microvascular endothelial cells grown in high glucose" Ye and Steinle, Mediators of Inflammation, 2016

"Src tyrosine kinase regulates the stem cell factor–induced breakdown of the blood–retinal barrier" Im et al. Molecular Vision, 2016

"Lymphoblastoid cell lines as a tool to study inter-individual differences in the response to glucose" Grassi et al. PLoS One, 2016

"Tenascin-C promotes angiogenesis in fibrovascular membranes in eyes with proliferative diabetic retinopathy" Kobayashi et al. Molecular Vision, 2016

"Retinal pericytes and cytomegalovirus infectivity: implications for HCMV-induced retinopathy and congenital ocular disease" Wilkerson et al. J Neuroinflammation, 2015

"Pigment epithelium-derived factor inhibits retinal microvascular dysfunction induced by 12/15-lipoxygenase-derived eicosanoids" Ibrahim et al. Biochim Biophys Acta, 2015

"Pioglitazone restores IGFBP-3 levels through DNA PK in retinal endothelial cells cultured in hyperglycemic conditions" Thakran et al. IOVS, 2015

"RNA-Seq reveals a role for NFAT-signaling in human retinal microvascular endothelial cells treated with TNFα" Savage et al. PLoS One, 2015

"miR-15b/16 protects primary human retinal microvascular endothelial cells against hyperglycemia-induced increases in tumor necrosis factor alpha and suppressor of cytokine signaling 3" Ye and Steinle, J Neuroinflammation, 2015

"The chemokine platelet factor-4 variant (PF-4var)/CXCL4L1 inhibits diabetes-induced blood–retinal barrier breakdown" Abu El-Asrar et al. IOVS, 2015

"Nuclear factor of activated T cells Is activated in the endothelium of retinal microvessels in diabetic mice" Zetterqvist et al. J Diabetes Research, 2015

"Noninvasive discrimination between human normal and cancer cells by analysis of intracellular distribution of phase-shift data" Takagi and Tokunaga, Cytotechnology, 2015

"Aflibercept traps galectin-1, an angiogenic factor associated with diabetic retinopathy" Kanda et al. Scientific Reports, 2015

"Slit2 signaling through Robo1 and Robo2 is required for retinal neovascularization" Rama et al. Nature Medicine, 2015

"Cyclic AMP response element binding protein mediates pathological retinal neovascularization via modulating DLL4-NOTCH1 Signaling" Singh et al. eBioMedicine, 2015

"Endothelial Snail regulates capillary branching morphogenesis via vascular endothelial growth factor receptor 3 expression" Park et al. PLoS Genetics, 2015

"Lignans from the stems and leaves of Brandisia hancei and their effects on VEGF-induced vascular permeability and migration of HRECs and DLAV formation in zebrafish" Lee et al, BBRC, 2014

"Metformin inhibits angiogenesis of human retinal vascular endothelial cells in vitro and in vivo" Han et al, IOVS, 2014

"Deletion of SPARC enhances retinal vaso-obliteration in mouse model of oxygen-induced retinopathy" Sobeih et al. HSOA Journal of Ophthalmology and Clinical Research, 2014

"A systems biology analysis of brain microvascular endothelial cell lipotoxicity" Aung et al. BMC Systems Biology, 2014

"TNFα inhibits IGFBP-3 through activation of p38α and casein kinase 2 in human retinal endothelial cells" Zhang et al. PLoS One, 2014

"STAT3 inhibition suppresses proliferation of retinoblastoma through down-regulation of positive feedback loop of STAT3/miR-17-92 clusters" Jo et al. Oncotarget, 2014

"Both Kdr and Flt1 play a vital role in hypoxia-induced Src-PLD1-PKCγ-cPLA2 activation and retinal neovascularization" Singh et al. Blood, 2013

"Insulin-like growth factor binding protein-3 inhibits monocyte adhesion to retinal endothelial cells in high glucose conditions" Zhang et al. Molecular Vision, 2013

"Interaction between pericytes and endothelial cells leads to formation of tight junction in hyaloid vessels" Jo et al. Molecules and Cells, 2013

"High-glucose-induced endothelial cell injury is inhibited by a peptide derived from human apolipoprotein E" Bhattacharjee et al. PLoS One, 2012

"Interactions between vitreous-derived cells and vascular endothelial cells in vitreoretinal diseases" Tojo et al. Acta Ophthalmologica, 2010

"Effect of infliximab on tumor necrosis factor-alpha-induced alterations in retinal microvascular endothelial cells and retinal pigment epithelial cells" Li et al, J Ocular Pharmacology and Therapeutics, 2010

"Additive effect of nicotine and hyperglycemia on upregulation of vascular endothelial growth factor and inflammation on human retinal pigment epithelial cells and retinal endothelial cells" Tirgan et al, IOVS, 2010

"The effects of nepafenac and amfenac on retinal angiogenesis" Yanni et al, Brain Research Bulletin, 2010

"TRAIL-deficient mice exhibit delayed regression of retinal neovascularization" Hubert et al, Am J Pathology, 2009

"Recruitment of pericytes and astrocytes is closely related to the formation of tight junction in developing retinal vessels" Kim et al. J Neuroscience Research, 2009

"Deguelin inhibits retinal neovascularization by down-regulation of HIF-1α in oxygen-induced retinopathy" Kim et al. Journal of Cellular and Molecular Medicine, 2008

"Beta-adrenergic receptor stimulation modulates iNOS protein levels through p38 and ERK1/2 signaling in human retinal endothelial cells" Steinle et al. Experimental Eye Research, 2008

"A novel role for activating transcription factor-2 in 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis" Zhao et al. J Lipid Research, 2008

"Interferon-beta and adhesion molecules (E-selectin and s-intracellular adhesion molecule-1) are detected in sera from patients with retinal vasculitis and are induced in retinal vascular endothelial cells by Toll-like receptor 3 signaling" Lee et al. Clinical Experiments in Immunology, 2007

"AKAP12 regulates human blood–retinal barrier formation by downregulation of hypoxia-inducible factor-1α" Choi et al. Journal of Neuroscience, 2007

"Sympathetic neurotransmission modulates expression of inflammatory markers in the rat retina" Steinle et al. Experimental Eye Research, 2007

"Brain endothelial hemostasis regulation by pericytes" Kim et al. Journal of Cerebral Blood Flow & Metabolism, 2006

"Tissue factor pathway inhibitor-2 is upregulated by vascular endothelial growth factor and suppresses growth factor-induced proliferation of endothelial cells" Xu et al. Arterioscler Thromb Vasc Biol. 2006

"Specific involvement of SRC family kinase activation in the pathogenesis of retinal neovascularization" Werdich and Penn, IOVS, 2006

"Susceptibility of retinal vascular endothelium to infection with Toxoplasma gondii tachyzoites" Smith et al. IOVS, 2004

"β3-adrenergic receptors regulate retinal endothelial cell migration and proliferation*" Steinle et al. J Biological Chemistry, 2003

"Constitutive and inflammatory mediator-regulated fractalkine expression in human ocular tissues and cultured cells" Silverman et al. IOVS, 2003
"A synthetic antagonist for the peroxisome proliferator-activated receptor gamma inhibits adipocyte differentiation" Wright et al. Journal of Biological Chemistry, 2000

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